Several clinical and tumour factors impact on ovarian cancer survival. It is important to evaluate if germline mutations impact long-term outcomes among patients with epithelial ovarian cancer.
We followed 1422 Ontario women with ovarian cancer. Clinical information was obtained from medical records and vital status was determined by registry linkage. Germline genetic testing was performed for 12 susceptibility genes. We estimated 20-year cancer-specific survival according to various factors.
Twenty-year survival was inferior for women with serous cancers vs. other types (22.3% vs. 68.6%; P < 0.0001). Of the 1422 patients, 248 (17.4%) carried a germline mutation; 119 BRCA1; 75 BRCA2; 7 in a mismatch repair (MMR) gene and 47 in one of seven other genes. Among serous patients, 20-year survival was 28.9% for similar for women with a BRCA1 (28.9%), BRCA2 (21.2%) or no mutation (21.6%). Among endometrioid patients, 20-year survival was poor for women with a BRCA vs. no mutation (47.3% vs. 70.4%; P = 0.004). Six of the seven MMR mutation carriers are currently alive, while all three PALB2 mutation carriers died within 3 years of diagnosis. Among women with Stage III/IV serous cancers, 20-year survival was 9.4% for those with vs. 46.5% for those with no residual disease (HR = 2.91; 95% CI 2.12–4.09, P < 0.0001).
The most important predictor of long-term survival was no residual disease post surgery. BRCA mutation status was not predictive of long-term survival while those with MMR mutations had excellent survival. Larger studies on PALB2 carriers are needed.
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Data underlying these analyses are not available in this manuscript, however, they are available through the authors or through dbGaP for the publicly available data.
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We acknowledge Isabel Fan for coordinating this study and the study participants for their involvement in this research study.
This study was supported by US National Institutes of Health grants R01-CA063678 (Narod); R01-CA063682 (Risch); and the Peter Gilgan Center for Women’s Cancers at Women’s College Hospital, in partnership with the Canadian Cancer Society. Joanne Kotsopoulos is a recipient of a Tier II Canada Research Chair. SAN is the recipient of a Tier I Canada Research Chair.
SAN is an editorial board member of BJC. The remaining authors declare no competing interests.
Ethics approval and consent to participate
All of the women provided written informed consent and the study was approved by the institutional review boards of the University of Toronto and Yale University. The study was performed in accordance with the Declaration of Helsinki.
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Kotsopoulos, J., Zamani, N., Rosen, B. et al. Impact of germline mutations in cancer-predisposing genes on long-term survival in patients with epithelial ovarian cancer. Br J Cancer 127, 879–885 (2022). https://doi.org/10.1038/s41416-022-01840-4